Malaria is considered as one of the most devastating global health problems due to the high morbidity and mortality it causes in the tropical parts of the world where it is endemic. Out of the 4 species that cause malaria in humans Plasmodium vivax is the most prevalent species outside tropical Africa. Although rarely fatal, P.vivax causes debilitating disease that severely affects the quality of life and economic productivity of the victims. In Sri Lanka, the main collaborating site for this study, malaria is endemic in 2/3rds of the country and is counted among the first four causes of hospital admissions in its endemic areas. Though both P.falciparum and P.vivax cause malaria in Sri Lanka, the latter species accounts for 70-80% or more of all malaria infections reported during the past decade. P.vivax genome sequence based on the the SAL-1 strain of P.vivax is almost complete and is available to the public (http:www.tigr.org/tdb/e2k1/pva1/). However, it does not provide any information on the genetic diversity or polymorphism of this parasite. Genetic variation is central to the pathogenesis of an organism and has significantly impeded progress towards the development of an effective malaria vaccine. Thus assessment of genetic diversity among parasite populations as proposed in this study has significant relevance for better understanding of its biology, for the development of strategies of disease control and to make valid estimations with regard to its origin. This study proposes an in depth analysis, including identification of single nucleotide polymorphisms (SNPs), in a 300 kb segment within the P.vivax genome by PCR-based sequencing of this region in 4 P.vivax strains with different geographical origins. Comparative genomic analysis together with the corresponding sequence in P.knowlesi, a closely related species to P.vivax is planned in addition to genotyping studies enabling the analysis of genome- wide microsatellite (MS) polymorphism and both MS and single nucleotide polymorphisms within the targeted region (300 kb) of a chromosome in patient isolates from varying geographical regions. This would enable the understanding of natural variation, population structure, genetic diversity and polymorphism, including the range of allele frequency spectrum and the patterns of linkage disequilibrium in recently archived field parasite isolates representing the global malaria endemic zones, which in turn would enable better understanding of the biology, population genetics and evolutionary history of this neglected parasite species. Malaria is one of the most important public health problems in many parts of world due to the high morbidity and mortality it causes, especially in young children. Better understanding of the genetic structure and its changes in the causative parasite, the objective of this proposed study, would enable the development of effective control strategies to combat this devastating disease that mostly affect the poor communities in the developing world.